Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have adopted policies beyond the WHO Framework Convention on Tobacco Control, which has been instrumental in reducing smoking prevalence. The impact of these policies (within and outside the Framework Convention on Tobacco Control) on smokeless tobacco use remains unclear. We aimed to systematically review policies that are relevant to smokeless tobacco and its context and investigate their impact on smokeless tobacco use. In this systematic review, we searched 11 electronic databases and grey literature between Jan 1, 2005, and Sept 20, 2021, in English and key south Asian languages, to summarise smokeless tobacco policies and their impact. Inclusion criteria were all types of studies on smokeless tobacco users that mentioned any smokeless tobacco relevant policies since 2005, except systematic reviews. Policies issued by organisations or private institutions were excluded as well as studies on e-cigarettes and Electronic Nicotine Delivery System except where harm reduction or switching were evaluated as a tobacco cessation strategy. Two reviewers independently screened articles, and data were extracted after standardisation. Quality of studies was appraised using the Effective Public Health Practice Project's Quality Assessment Tool. Outcomes for impact assessment included smokeless tobacco prevalence, uptake, cessation, and health effects. Due to substantial heterogeneity in the descriptions of policies and outcomes, data were descriptively and narratively synthesised. This systematic review was registered in PROSPERO (CRD42020191946). 14 317 records were identified, of which 252 eligible studies were included as describing smokeless tobacco policies. 57 countries had policies targeting smokeless tobacco, of which 17 had policies outside the Framework Convention on Tobacco Control for smokeless tobacco (eg, spitting bans). 18 studies evaluated the impact, which were of variable quality (six strong, seven moderate, and five weak) and reported mainly on prevalence of smokeless tobacco use. The body of work evaluating policy initiatives based on the Framework Convention on Tobacco Control found that these initiatives were associated with reductions in smokeless tobacco prevalence of between 4·4% and 30·3% for taxation and 22·2% and 70·9% for multifaceted policies. Two studies evaluating the non-Framework policy of sales bans reported significant reductions in smokeless tobacco sale (6·4%) and use (combined sex 17·6%); one study, however, reported an increased trend in smokeless tobacco use in the youth after a total sales ban, likely due to cross-border smuggling. The one study reporting on cessation found a 13·3% increase in quit attempts in individuals exposed (47·5%) to Framework Convention on Tobacco Control policy: education, communication, training, and public awareness, compared with non-exposed (34·2%). Many countries have implemented smokeless tobacco control policies, including those that extend beyond the Framework Convention on Tobacco Control. The available evidence suggests that taxation and multifaceted policy initiatives are associated with meaningful reductions in smokeless tobacco use. UK National Institute for Health Research.